Future potential targets of antibody-drug conjugates in breast cancer
Metastatic breast cancer (BC) remains an incurable disease. Besides endocrine and targeted agents, chemotherapy is still a relevant therapeutic option for this disease. Recently, antibody-drug conjugates (ADCs) have shown to overcome the lack of tumor specificity and systemic toxicity typically asso...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Breast |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0960977623004241 |
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| author | Chiara Corti Luca Boscolo Bielo Ambra Carnevale Schianca Beatrice Taurelli Salimbeni Carmen Criscitiello Giuseppe Curigliano |
| author_facet | Chiara Corti Luca Boscolo Bielo Ambra Carnevale Schianca Beatrice Taurelli Salimbeni Carmen Criscitiello Giuseppe Curigliano |
| author_sort | Chiara Corti |
| collection | DOAJ |
| description | Metastatic breast cancer (BC) remains an incurable disease. Besides endocrine and targeted agents, chemotherapy is still a relevant therapeutic option for this disease. Recently, antibody-drug conjugates (ADCs) have shown to overcome the lack of tumor specificity and systemic toxicity typically associated with traditional chemotherapies, thus improving the therapeutic index. To effectively exploit this technological breakthrough, identification of optimal target antigens (Ags) is of utmost importance. To make the ideal target, differential expression of target Ags between healthy and cancer tissues, as well as specific mechanisms of ADC internalization after Ag-antibody interaction are required.Therefore, several in silico strategies to identify and characterize new promising candidate Ags have been developed. If initial in vitro and in vivo positive data are documented, thus providing a biological rationale for further Ag investigation, early phase clinical trials are designed. In BC, these strategies have already led to the development of effective ADCs, namely trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), primarily targeting HER2 and TROP-2. However, promising new Ags are currently under investigation, with encouraging results especially coming from targeting HER3, FRα, Tissue Factor, LIV-1, ROR1-2, and B7–H4.In this review, we describe the landscape of emergent and future potential targets (i.e., other than HER2 and TROP-2) investigated in BC for ADC development. Predominant target expression, function, preclinical rationale, potential clinical implication, as well as preliminary clinical trial results are provided. |
| first_indexed | 2024-03-13T05:40:35Z |
| format | Article |
| id | doaj.art-57d28d321ac548019dafa95bf30496ab |
| institution | Directory Open Access Journal |
| issn | 1532-3080 |
| language | English |
| last_indexed | 2024-03-13T05:40:35Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Breast |
| spelling | doaj.art-57d28d321ac548019dafa95bf30496ab2023-06-14T04:32:40ZengElsevierBreast1532-30802023-06-0169312322Future potential targets of antibody-drug conjugates in breast cancerChiara Corti0Luca Boscolo Bielo1Ambra Carnevale Schianca2Beatrice Taurelli Salimbeni3Carmen Criscitiello4Giuseppe Curigliano5Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology (DIPO), University of Milan, Milan, Italy; Corresponding author. Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141, Milan, Italy.Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology (DIPO), University of Milan, Milan, ItalyDivision of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology (DIPO), University of Milan, Milan, ItalyDivision of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology (DIPO), University of Milan, Milan, ItalyDivision of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology (DIPO), University of Milan, Milan, ItalyDivision of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology (DIPO), University of Milan, Milan, ItalyMetastatic breast cancer (BC) remains an incurable disease. Besides endocrine and targeted agents, chemotherapy is still a relevant therapeutic option for this disease. Recently, antibody-drug conjugates (ADCs) have shown to overcome the lack of tumor specificity and systemic toxicity typically associated with traditional chemotherapies, thus improving the therapeutic index. To effectively exploit this technological breakthrough, identification of optimal target antigens (Ags) is of utmost importance. To make the ideal target, differential expression of target Ags between healthy and cancer tissues, as well as specific mechanisms of ADC internalization after Ag-antibody interaction are required.Therefore, several in silico strategies to identify and characterize new promising candidate Ags have been developed. If initial in vitro and in vivo positive data are documented, thus providing a biological rationale for further Ag investigation, early phase clinical trials are designed. In BC, these strategies have already led to the development of effective ADCs, namely trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), primarily targeting HER2 and TROP-2. However, promising new Ags are currently under investigation, with encouraging results especially coming from targeting HER3, FRα, Tissue Factor, LIV-1, ROR1-2, and B7–H4.In this review, we describe the landscape of emergent and future potential targets (i.e., other than HER2 and TROP-2) investigated in BC for ADC development. Predominant target expression, function, preclinical rationale, potential clinical implication, as well as preliminary clinical trial results are provided.http://www.sciencedirect.com/science/article/pii/S0960977623004241Antibody-drug conjugateDrug developmentEarly phaseAntigenBiomarkerBreast cancer |
| spellingShingle | Chiara Corti Luca Boscolo Bielo Ambra Carnevale Schianca Beatrice Taurelli Salimbeni Carmen Criscitiello Giuseppe Curigliano Future potential targets of antibody-drug conjugates in breast cancer Breast Antibody-drug conjugate Drug development Early phase Antigen Biomarker Breast cancer |
| title | Future potential targets of antibody-drug conjugates in breast cancer |
| title_full | Future potential targets of antibody-drug conjugates in breast cancer |
| title_fullStr | Future potential targets of antibody-drug conjugates in breast cancer |
| title_full_unstemmed | Future potential targets of antibody-drug conjugates in breast cancer |
| title_short | Future potential targets of antibody-drug conjugates in breast cancer |
| title_sort | future potential targets of antibody drug conjugates in breast cancer |
| topic | Antibody-drug conjugate Drug development Early phase Antigen Biomarker Breast cancer |
| url | http://www.sciencedirect.com/science/article/pii/S0960977623004241 |
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